Topiramate and Schizophrenia: Effects on Weight and Psychopathology
關鍵詞
抽象
描述
Schizophrenia is a chronic illness characterized by social and vocational disruptive functioning. While >70% of individuals with first episode illness respond to antipsychotics (APs), there remains a subgroup left with persisting psychotic symptoms. For these individuals, clozapine (CLZ) is also the sole drug with treatment superiority, but also carries the greatest metabolic liability. Another complicating factor in those treated with CLZ is the observation that while effective in some, 40-70% of individuals fail to show significant improvement with CLZ, often leading to augmentation strategies. While controlled trials are, in general lacking, a number of agents have been suggested as useful. One such group of medications includes the anticonvulsants.
Topiramate represents one of the newer anticonvulsant agents approved for the treatment of epilepsy and prophylaxis of migraines. Importantly, topiramate possesses a weight-reducing effect that has been substantiated by a meta-analysis in non-psychiatric patients. Interestingly, topiramate has been studied as an adjunctive therapy in treatment-resistant schizophrenia with some evidence demonstrating small to moderate benefits with topiramate augmentation on psychopathology. However, these benefits must also be weighed against reports (primarily from epilepsy populations), that topiramate may cause cognitive dysfunction.
This study will examine:
1. Topiramate-related effects on weight
2. Topiramate-related effects on glucose tolerance and insulin sensitivity
3. Topiramate-related effects on psychopathology and cognition
4. Topiramate-related effects on adiposity
日期
| 最後驗證: | 12/31/2019 |
| 首次提交: | 06/14/2016 |
| 提交的預估入學人數: | 06/16/2016 |
| 首次發布: | 06/20/2016 |
| 上次提交的更新: | 01/05/2020 |
| 最近更新發布: | 01/08/2020 |
| 實際學習開始日期: | 04/30/2016 |
| 預計主要完成日期: | 02/28/2021 |
| 預計完成日期: | 02/28/2021 |
狀況或疾病
干預/治療
Drug: Topiramate
Other: Placebo
相
手臂組
| 臂 | 干預/治療 |
|---|---|
| Experimental: Topiramate Topiramate will be dispensed on a biweekly basis, and pill counts conducted at each visit. | Drug: Topiramate Topiramate capsules starting with 25 mg b.i.d with an incremental increase of 25 mg b.i.d weekly upto a maximum of 100 mg b.i.d. |
| Placebo Comparator: Placebo Placebo will be dispensed on a biweekly basis, and pill counts conducted at each visit. | Other: Placebo Placebo capsules visually identical to those containing topiramate will be administered. |
資格標準
| 有資格學習的年齡 | 17 Years 至 17 Years |
| 有資格學習的性別 | All |
| 接受健康志願者 | 是 |
| 標準 | Inclusion Criteria: - Schizophrenia or Schizoaffective disorder - 17-59 years of age - Clozapine treatment for at least 12 weeks at a dose 350 mg/d or greater and/or plasma clozapine levels of 300 ng/mL or greater - CGI must be 4 or higher and/or GAF < 50 - BMI greater than or equal to 25 Exclusion Criteria: - Alcohol use disorder - Patients with liver, or renal dysfunction - Females of child bearing age not on a regular contraceptive, females who are nursing - Clinical or laboratory evidence of uncompensated cardiovascular, endocrine, hematological, or pulmonary disease. - HbA1c > 9%, or symptomatic hyperglycemia with metabolic decompensation - Prior lack of efficacy or tolerability of Topiramate - Addition of new hypoglycemic or lipid lowering medication within 2 months of starting study - Patients treated with Valproic Acid - Patients treated with hydrochlorothiazide - Switch in antipsychotic medications within 3 months of study entry - Major medical or surgical event within the preceding 3 months - History of renal stones - Use of Carbonic Anhydrase Inhibitor - History of glaucoma - Acute Suicidal risk |
結果
主要結果指標
1. Weight loss [16 weeks]
次要成果指標
1. Insulin sensitivity [16 weeks]
2. Psychopathology - Positive and Negative Syndrome Scale (PANSS) [16 weeks]
3. Glucose Tolerance [16 weeks]
4. Psychopathology - Brief Psychiatric Rating Scale (BPRS) [16 weeks]
5. Psychopathology - Clinical Global Impression (CGI) [16 weeks]
6. Psychopathology - Global Assessment of Functioning (GAF) [16 weeks]
其他成果措施
1. Visceral adiposity changes [Baseline and 16 weeks]
2. Cognition - Brief Assessment of Cognition in Schizophrenia (BACS) [16 weeks]
3. Volumetric Brain changes [Baseline and 16 weeks]
4. Hepatic adiposity changes [Baseline and 16 weeks]
